The present invention concerns a specific composition comprised of a mixture of gangliosides and of its single fractions which have proved to have a protective effect in neurotoxicity caused by anti-blastics.
Gangliosides represent a family of complex glycolipid molecules, natural components of cellular membranes, and in particular of the neuronal membranes, involved in the processes of development, differentiation and neuronal regeneration.
Exogenous gangliosides are incorporated into the neuronal membranes in a stable manner (Toffano G. et al. (1980): J. Neurochem. 35, (4), 861-866; Aporti F. et al. (1981): Acta Oto-Laryingologica, 92. 433-437). This incorporation is associated with the activation of an enzymatic membrane system, (Na.sup.+, K.sup.+)ATPase, the activity of which is essential for nervous impulse conduction. Enzymatic incorporation and activation have been demonstrated both in vitro (Leon A. et al. (1981): J. Neurochem. 37, (2), 350-357) and in vivo (Aporti F. et al. (1981)).
Gangliosides are acid glycolipids belonging to the family of biological compounds known as glycosphingolipids. These comprise 4 basic structural units: one long aminoalcohol chain, one fatty acid, one oligosaccharide fraction and one or more sialic acid residues.
The long amino alcohol chain, present in cerebral gangliosides is identifiable as 4-sphingenine and its longest chain analogue as 4-eicosasphingenine; These compounds are commonly known as sphingosines. ##STR1## The corresponding saturated compounds (sphinganines) are also present in gangliosides in smaller proportions.
A fatty acid is bound by an amidic bond to the basic sphingosine. In cerebral gangliosides this fatty acid is 95% stearic acid (18:0). Other fatty acids are found in smaller proportions, for example arachidic acid (20:0), palmitic acid (16:0) or palmitoleic acid (16:1.sup.9). The amino alcohol and fatty acid together form a unit called a Ceramide, which represents the hydrophobic part of the ganglioside molecule.
The oligosaccharide chain bound to the ceramide characterizes the vaste family of glycosphingolipids to which gangliosides belong. Sphingolipids are classified in two subgroups, based on carbohydrates immediately bound to the ceramide. The first and smallest subgroup derives from galactosylceramide. Most glycosphingolipids, and therefore virtually all gangliosides, belong to the subgroup derived from glucosylceramide.
Sialic acid is present in cerebral gangliosides mainly in N-acetyl form, but the N-glycolyl form has been identified in some ganglioside species. This residue is generally known as neuraminic acid (NANA or NGNA). ##STR2## The hydrophilicity of gangliosides is due to the oligosaccharide chain and to the number of sialic residues bound to this chain.